Across the globe, unprecedented declines have been reported across a range of taxa. Among the most well documented are declines in bird populations, with most declines attributable to human activities such as deforestation and other alterations to habitats. There is increasing evidence that bird populations also have declined at sites within large expanses of relatively undisturbed lowland tropical forest, such as in Amazonia. Causes of such declines likely are varied and may be related to direct or indirect effects of climate change. Here, we use mist-net data and direct observations to examine changes in bird numbers over a 22-yr period on two 100-ha study plots in an Amazonian lowland forest of eastern Ecuador. As previously reported, capture rates experienced large declines from 2009 on; observation rates also showed large declines through 2013 but subsequently have shown no consistent trend up or down. Overall capture rates and observation rates are now approximately half the rates during the first decade. Most foraging guilds also declined over time, with declines particularly pronounced among insectivorous groups. With few exceptions, patterns of change were similar between plots suggesting a more general response rather than responses to local factors on each plot. Capture rates and observation rates of ∼90% of the most common species in both understory and canopy were lower during the latter part of the study, with only a few species (∼10%) showing increases. Similarly, large declines were seen in both canopy and understory mixed-species flocks. Large declines in bird numbers have been noted in other tropical sites that have conducted long-term population studies, including Panama and Brazil, suggesting a response to large-scale factors, such as climate change. While not yet documented, the consequences of losing approximately 50% of population abundance are likely substantial and could result in local extinction of rare species, altered species interactions and social organization, as well as declining ecological function and biotic integrity of these tropical forest ecosystems.